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EX'TOXNET PIP - 2,4-D Page 2 of 3 . Reproductive effects: High levels of 2,4-D (about 50 mg/kg/day) administered orally to pregnant rats did not cause any adverse effects on birth weights or litter size. Higher doses (188 mg/kg/day) resulted in fetuses with abdominal cavity bleeding and increased mortality [1,5,7]. DNA synthesis in the testes was significantly inhibited when mice were fed large amounts (200 mg/kg/day) of 2,4-D [7]. The evidence suggests that if 2,4- D causes reproductive effects in animals,this only occurs at very high doses. Thus reproductive problems associated with 2,4-D are unlikely in humans under normal circumstances. . Teratogenic effects: 2,4-D may cause birth defects at high doses. Rats fed 150 mg/kg/day on days 6 to 15 of pregnancy had offspring with increased skeletal abnormalities, such as delayed bone development and wavy ribs [7]. This suggests that 2,4-D exposure is unlikely to be teratogenic in humans at expected exposure levels. . Mutagenic effects: 2,4-D.has been very extensively tested and was found to be nonmutagenic in most systems. 2,4-D did not damage DNA in human lung cells. However, in one study, significant effects occurred in chromosomes in cultured human cells at low exposure levels [26]. The data suggest that 2,4-D is not mutagenic or has low mutagenic potential. . Carcinogenic effects: 2,4-D fed to rats for 2 years caused an increase in malignant tumors [7]. Female mice given a single injection of 2,4-D developed cancer(reticulum-cell sarcomas) [7]. Another study in rodents shows a low incidence of brain tumors at moderate exposure levels (45 mg/kg/day) over a lifetime [1,7]. However, a number of questions have been raised about the validity of this evidence and thus about the carcinogenic potential of 2,4-D. In humans, a variety of studies give conflicting results. Several studies suggest an association of 2,4-D exposure with cancer. An increased occurrence of non-Hodgkin's lymphoma was found among a Kansas and Nebraska farm population associated with the spraying of 2,4-D [25,27]. Other studies done in New Zealand, Washington,New York, Australia, and on Vietnam veterans from the U.S. were all negative. There remains considerable controversy about the methods used in the various studies and their results [28]. Thus, the carcinogenic status of 2,4-D is not clear. . Organ toxicity: Most symptoms of 2,4-D exposure disappear within a few days, but there is a report of liver dysfunction from long-term exposure [1,25]. . Fate in humans and animals: The absorption of 2,4-D is almost complete in mammals after ingestion and nearly all of the dose is excreted in the urine. The compound is readily absorbed through the skin and lungs. Men given 5 mg/kg excreted about $2/ of the dose as unchanged 2,4-D. The half-life is between 10 and 20 I� hours in living organisms. There is no evidence that 2,4-D accumulates to significant level in mammals or in g other organisms [20]. Between 6 and 8 hours after doses of 1 mg/kg, peak concentrations of 2,4-D were found in the blood, liver, kidney, lungs, and spleen of rats. There were lower levels in muscle and brain. After 24 hours, there were no detectable tissue residues. Only traces of the compound have been found in the milk of lactating animals for 6 days following exposure. 2,4-D passes through the placenta in pigs and rats. In rats, about 20% was detected in the uterus, placenta, fetus, and amniotic fluid [27]. Chickens given moderate amounts of 2,4-D in drinking water from birth to maturity had very low levels of the compound in eggs [7]. Ecolo lcal Effects: . Effects on birds: 2,4-D is slightly toxic to wildfowl and slightly to moderately toxic to birds. The LD50 is 1000 mg/kg in mallards, 272 mg/kg in pheasants, and 668 mg/kg in quail and pigeons [5-7]. . Effects on aquatic organisms: Some formulations of 2,4-D are highly toxic to fish while others are less so. For example", the LC50 ranges between 1.0 and 100 mg/L in cutthroat trout, depending on the formulation used. Channel catfish had less than 10% mortality when exposed to 10 mg/L for 48 hours [1,9]. Green sunfish, when exposed to 110 mg/L for 41 hours, showed no effect on swimming response. Limited studies indicate a half-life of less than 2 days in fish and oysters [24]. Concentrations of 10 mg/L for 85 days did not adversely affect the survival of adult dun eness crabs. For immature crabs the 96-hour LC50 is greater than 10 mg/L, a g indicating that 2,4-D is only slightly toxic. Brown shrimp showed a small increase in mortality at exposures of 2 mg/L for 48 hours [7,20]. . Effects on other organisms: Moderate doses of 2,4-D severely impaired honeybees brood production. At lower levels of exposure, exposed bees lived significantly longer than the controls. The honeybee LD50 is 0.0115 mg/bee [6,7]. Environmental'Fate: . (Breakdown Yn soil and gi ound ' aterc 2,4-D has low soil persistence. The half-life in soil is less than 7 days [21]. Soil microbes are primarily responsible for its disappearance [20]. Despite its short half-life in soil and in aquatic environments, the compound has been detected in groundwater supplies in at least five States and in i Canada [20]. Very low concentrations have also been detected in surface waters throughout the U.S. [23]. . Breakdown in-water: In aquatic environments, microorganisms readily degrade 2,4-D. Rates of breakdown